This invention relates to a new agent with antimetastatic action.
After application of prostacyclin (PGI.sub.2) in high dosage (10 mg/kg) shortly before intravenous injection of tumor cells of B16 mouse melanoma, K. V. Honn et al. [Science 212, 1270 (1981)] observed a reduction of the number of lung metastases. This action is ascribed to an inhibition of the tumor cell adhesion and aggregation. But for an application the half-life is too short and the dose of PGI.sub.2 is too high. Therefore, with the more stable prostacylin analog, Iloprost, a pharmaceutical application would be more conceivable.
V. costantini et al. (Cancer Chemother. Pharmacol. 22, 289 (1988) compared the antimetastatic action of PGI.sub.2 (5 and 10 mg/kg) and Iloprost (0.1 and 0.2 mg/kg) on the formation of lung metastases of the melanoma cell line BLG after intravenous injection of the tumor cells in mice. The action was a function of the number of applied tumor cells and the periods between substance and tumor cell application. In various test arrangements, Iloprost proved to be clearly superior to PGI.sub.2 from the dose, the duration of action and the achieved inhibition action.
Piccini et al. (1988) obtained comparable data on the Lewis lung carcinoma of the mouse by use of the same dosages and similar test arrangements. In a one-time dose of 0.2 mg/kg, 1 hour before injection of the tumor cells, Iloprost reduced the number of lung metastases by more than 90%.
But test arrangements such as intravenous injection of tumor cells or one-time substance administration clinically have little relevance.
Another test described by Piccini et al. is more meaningful. In a standard model for establishing an antimetastatic potency, namely i.m. implantation of a primary tumor (Lewis lung carcinoma) in the leg and subsequent surgical removal of the tumor (leg amputation), Iloprost (0.2 mg/kg, 1.5 hours before tumor removal) reduced the number of lung metastases by about 50%. But the survival time was only insignificantly lengthened.